Leaflet: information for the user

Entonox 50%/50% medicinal gas, tablet

Nitrous oxide / Oxygen

Read this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

1. What Entonox is and for what it is used

2. What you need to know before starting to use Entonox

3. How to use Entonox

4. Possible side effects

5. Storage of Entonox

6. Contents of the pack and additional information

Entonox is a prepared mixture of nitrous oxide ("laughing gas," N2O) and oxygen (medical oxygen, O2), 50% of each, and must be used by breathing the gas mixture.

The effects of Entonox:

Nitrous oxide constitutes 50% of the gas mixture. Nitrous oxide has an analgesic effect, reduces the sensation of pain, and increases the pain threshold. Nitrous oxide also has a relaxing and slightly calming effect. These effects occur due to the action of nitrous oxide on substances that send signals in your nervous system.

The concentration of 50 percent oxygen, around double that found in ambient air, ensures a safe oxygen content in the inhaled gas.

What is Entonox used for

Entonox should be used when an analgesic effect and a quick remedy for moderate intensity and limited duration pain are desired. Entonox produces analgesic effect after a few inhalations and this effect ceases in minutes upon stopping use. Entonox can be used in adults and in children from 1 month of age.

No use Entonox:

Before using Entonox, inform your doctor if you have any of the following symptoms:

•Bubbles in cavities or gas-filled cavities:If due to a disease or any other reason, you suspect there is air in your pleural cavities outside the lungs, or gas bubbles in the blood, or in any other organ (for example, if you have been scuba diving and may have gas bubbles in the blood; or if you have received an intraocular gas injection, for example, due to a retinal detachment, or similar) these gas bubbles may expand and cause damage.

•Heart disease:If you have heart failure or a poorly functioning heart, as the mild relaxing effect of nitrous oxide on heart muscle may further impair its functioning.

•Central nervous system injury:If you have high blood pressure, for example, as a result of a tumor or cerebral hemorrhage, nitrous oxide may increase blood pressure in the brain with potential risk of damage.

•Vitamin deficiency:If you have a diagnosed but untreated vitamin B12 deficiency, or a deficiency of folic acid, the use of nitrous oxide may worsen the symptoms caused by vitamin B12 and folic acid deficiency.

•Intestinal pseudo-obstruction (ileus or ileus):If you have severe abdominal discomfort: if there are symptoms that may indicate ileus, Entonox may increase intestinal dilation.

•Face or jaw injuries:when the use of a face mask may present difficulties or risks.

Warnings and precautions:

Also consult your doctor if you have any of the following signs or symptoms:

• Decreased level of consciousness or persistent signs of confusion: Inform your doctor if you do not feel well or feel that due to a trauma or disease you are not fully awake. This is important due to the sedative effects of nitrous oxide in Entonox. There is a risk of excessive sedation that may affect your natural protective reflexes.

• Ear discomfort: for example, inflammation of the ear, as Entonox may increase pressure in the middle ear.

• Chronic obstructive pulmonary disease (COPD), as oxygen may cause respiratory depression.

• If you have a history of medication abuse, as there is a high risk of generating dependence on nitrous oxide if you take it repeatedly. Your doctor will decide if nitrous oxide treatment is possible in your case.

• Vitamin deficiency: if you suspect you have a vitamin B12 deficiency or a deficiency of folic acid, as the use of nitrous oxide may worsen the symptoms caused by vitamin B12 and folic acid deficiency.

Your doctor will decide if it is advisable to use Entonox.

Prolonged or repeated use of nitrous oxide may increase the risk of vitamin B12 deficiency, which may trigger damage to the bone marrow or nervous system. Your doctor may require blood tests before and after treatment. Your doctor may require a blood test before and after treatment with the aim of evaluating the consequences of a possible vitamin B12 deficiency.

Use of Entonox with other medications:

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

• Methotrexate for the treatment of arthritis. The concurrent administration of Entonox with methotrexate may affect blood cell count.

If you are taking other medications that affect the brain or brain functions, for example, benzodiazepines (tranquilizers) or morphine, you must inform your doctor. Entonox may increase the effects of these medications. Entonox, taken together with other sedatives or medications that affect the central nervous system, increases the risk of side effects.

• Bleomycin (for cancer treatment) or amiodarone (to treat irregular heartbeat), before taking Entonox as there is a possibility of toxic effects on the lungs due to high oxygen concentration.
• Nitrofurantoin or similar antibiotics (to treat infections).

Pregnancy, breastfeeding, and fertility:

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or nurse before using this medication.

Entonox can be used during pregnancy if your doctor considers it clinically necessary. It can also be used during childbirth. If used near childbirth, your baby should be observed to detect respiratory difficulties (respiratory depression) and other adverse effects.

Entonox can be used during breastfeeding, but it should not be used at the time of breastfeeding.

Driving and operating machinery:

It is essential to note that after administration of Entonox, recovery is necessary. Nitrous oxide in Entonox disappears from the body quickly with brief inhalations. Effects on cognitive abilities (consciousness) may last for several hours. For safety reasons, you should avoid driving, operating machinery, or performing complex tasks until you have fully recovered (at least 30 minutes).

Ensure that the healthcare professional informs you if it is safe for you to drive.

Entonox must be administered at all times in the presence of personnel familiar with this type of medication. During the period in which you use Entonox, both you and the medication administration must be monitored to ensure that it is administered safely. After completing treatment, you must be monitored by competent personnel until you have recovered.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor again. Your doctor or nurse must explain to you how to use Entonox, how Entonox works, and what effects result from its use.

Entonox is normally inhaled through a mask attached to a special valve, having full control of the gas flow through your own breathing. The valve is only open during inspiration. Entonox can also be administered with a nasal mask. Regardless of which mask is used, you must breathe normally.

Use in children

In children who are not able to understand and follow instructions, Entonox must be administered under the supervision of competent medical personnel who can help them keep the mask in place and actively monitor the administration. In these cases, Entonox can be administered with a continuous gas flow.

After stopping the use of Entonox, you must rest and recover until you feel mentally recovered.

Safety measures:

• Smoking and the presence of flames are strictly prohibited in the room where the treatment with Entonox takes place.

• Entonox is exclusively for medicinal use

Please also review the instructions for handling and storage of Entonox (5. Storage of Entonox).

If you use more Entonox than you should:

It is unlikely that you will receive too much gas, since you control the application of gas and the gas mixture is fixed (with 50% nitrous oxide and 50% oxygen).

If you breathe more quickly than normal, receiving more nitrous oxide than with normal breathing, you may feel noticeably tired and lose some contact with your surroundings. In this case, you must immediately inform the medical personnel and stop using it.

If you have any additional questions about the use of this medication, ask your doctor or nurse.

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone 91 562 04 20.

Like all medications, this medication may produce adverse effects, although not everyone will experience them.

Frequent(may affect up to 1 in 10 users):

Dizziness, drowsiness, euphoria, nausea, and vomiting.

Infrequent(may affect up to 1 in 100 users):

Severe fatigue. Feeling of pressure in the middle ear, if Entonox is used for a prolonged period. This is due to Entonox increasing pressure in the middle ear. Abdominal distension, because Entonox slowly increases the volume of intestinal gases.

Unknown frequency(cannot be estimated from available data):

Effects on the nervous system, numbness, and weakness, usually in the legs.

Effects on the bone marrow, which may cause anemia (low red blood cell count) and leucopenia (low white blood cell count).

You may also experience headaches and confusion after stopping administration.

Psychiatric effects have been reported in extremely rare cases, such as psychosis, confusion, and anxiety. Respiratory depression.

Dependence.

Generalized seizures.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use. Website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging.

Do not store it at a temperature below -5°C.

If you suspect that Entonox has been stored in conditions that are too cold, the cylinders should be placed in a horizontal position at a temperature greater than +10°C for at least 48 hours before use.

Store the cylinder in a designated storage area for medical gases.

It should be kept away from flammable materials. It should only be used in well-ventilated areas.

Do not smoke near it or expose it to strong heat.

If there is a risk of fire, the Entonox cylinder should be moved to a safe location.

Keep the cylinder clean, dry, and free of oil and grease.

Ensure that the cylinder has not been subjected to any impact or fallen.

It should be stored and transported with the valves closed.

The vapor may cause drowsiness and dizziness.

Composition of Entonox

- The active substances are:

nitrous oxide 50% = medicinal laughing gas (chemical term: N2O) and

oxygen 50% = medicinal oxygen (chemical term: O2)

- Entonox does not contain any other ingredient

Appearance of the product and contents of the container

Entonox is an odorless, tasteless, colorless gas that is supplied in a cylinder with a valve to control the flow of gas.

Pharmaceutical form: medicinal gas, compressed.

The top of the cylinder is marked in white and blue (oxygen/nitrous oxide). The body of the cylinder is white (medicinal gas).

Not all sizes of containers are marketed.

Holder of the marketing authorization:

Linde Sverige AB

Rättarvägen 3

169 68 Solna

Sweden

Manufacturers responsible::

AGA Gas AB

Rotevägen 2

SE- 192 78 Sollentuna (site Rotebro)

Sweden

Linde Gas AB

Baltzar von Platens gata 4-6

SE-74521 Enköping

Sweden

Linde France

16 avenue de la Saudrune

Industrial zone du Bois Vert

31 120 Portet sur Garonne

France

Linde Gaz Polska Sp. Z o.o.

ul. Zwirowa 4

33-100 Tarnów

Poland

LINDE GAZ POLSKA Sp. Z o. o.

Branch in Tarnów

Poland

Information provided by:

LINDE GAS ESPAÑA, SA.U.

C/ Camino de Liria, s/n, post office box nº 25,

46530 Puzol, Valencia, Spain

Tel: 902 426 462

This medicinal product is authorized in the Member States of the EEA under the following names:

Austria LIVOPAN

Belgium RELIVOPAN

Czech Republic ENTONOX

Cyprus ENTONOX

Denmark LIVOPAN

Estonia ENTONOX

Finland LIVOPAN

Germany LIVOPAN

Greece ENTONOX

Hungary ENTONOX

Iceland LIVOPAN

Italy LIVOPAN

Latvia ENTONOX

Lithuania ENTONOX

Luxembourg RELIVOPAN

Netherlands RELIVOPAN

Norway LIVOPAN

Poland ENTONOX

Portugal LIVOPAN

Romania ENTONOX

Spain ENTONOX

Slovakia ENTONOX

Sweden LIVOPAN

Date of the last review of this leaflet:May 2019

Other sources of information

The detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices: www.aemps.es

-------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Safety instructions

No adverse effects on the fetus have been observed in women occupationally exposed to chronic inhalation of nitrous oxide during pregnancy when a suitable ventilation and air renewal system is available. Please see the technical data sheet for more information. Special precautions should be taken when working with nitrous oxide. Nitrous oxide should be administered according to local guidelines.

Entonox should only be used in well-ventilated areas with special equipment for removing excess gas. Using an extractor system and ensuring good ventilation, high concentrations of anesthetic gas in the ambient air are avoided. High concentrations of anesthetic gas in the air can cause adverse health effects on personnel and people in the surrounding area. National values for the concentration of nitrous oxide in the air should not exceed the so-called "safe limits", often expressed as: TWA (time-weighted average or time-weighted average), which is the average value over a working day, and STEL (short-term exposure limit or short-term exposure limit), which is the average value over a shorter exposure period.

These values should not be exceeded to ensure that personnel are not exposed to risks.

Repeated administration or exposure to nitrous oxide may lead to addiction. Caution should be exercised in healthcare professionals with occupational exposure to nitrous oxide.

• The valve should be opened slowly and carefully.

• Turn off the equipment in case of fire, or if it is not functioning.

• During the use of the cylinder, it should be secured with a suitable support.

• The cylinder should be replaced when the pressure has dropped to a point where the indicator on the valve is within the yellow field.

• When there is a small amount of gas left in the cylinder, the valve should be closed. It is essential to leave a little pressure in the cylinder to prevent the entry of contaminants.

• After use, the valve on the cylinder should be closed firmly. Depressurize the regulator or connection.